M1/M2-macrophage phenotypes regulate renal calcium oxalate crystal development

In our previous report, M2-macrophage (M phi s) deficient mice showed increased renal calcium oxalate (CaOx) crystal formation; however, the role of M phi s-related-cytokines and chemokines that affect kidney stone formation remains unknown. Here, we investigated the role of M1/M2s in crystal development by using in vitro and in vivo approaches. The crystal phagocytic rate of bone marrow-derived M2M phi s was higher than that of bone marrow-derived M phi s and M1M phi s and increased on co-culture with renal tubular cells (RTCs). However, the amount of crystal attachment on RTCs reduced on co-culture with M2M phi s In six hyperoxaluric C57BL/6J mice, M1M phi transfusion and induction by LPS and IFN-gamma facilitated renal crystal formation, whereas M2M phi transfusion and induction by IL-4 and IL-13 suppressed renal crystal formation compared with the control. These M2M phi treatments reduced the expression of crystal-related genes, such as osteopontin and CD44, whereas M1M phi treatment increased the expression of pro-inflammatory and adhesion-related genes such as IL-6, inducible NOS, TNF-alpha, C3, and VCAM-1. The expression of M2M phi-related genes was lower whereas that of M1M phi-related genes was higher in papillary tissue of CaOx stone formers. Overall, our results suggest that renal crystal development is facilitated by M1M phi s, but suppressed by M2M phi s.